Domestic violence is a problem of major proportions in the United States. The majority of studies pertaining to the etiology of domestic violence have focused on psychosocial parameters and given little emphasis to biological factors. In order to explore the possiblity that the aggression displayed by perpetrators is related to fear, we administered the panicogenic agent, sodium lactate, to a select group of perpetrators. Results of this study showed that perpetrators evidenced more lactate-induced fear, panic, and rage than non-violent controls. These results lead us to conclude that some perpetrators of domestic violence have an exaggerated fear-related rage response to perceived threats. Our current research is directed toward understanding what abnormality(s) may be present in perpetrators which could contribute to these exaggerated fear-related responses. To do this, we are conducting a number of research studies. We performed detailed psychiatric evaluations of perpetrators and controls. Preliminary results indicate that perpetrators have a higher incidence of anxiety-related disorders than expected. We obtained cerebral spinal fluid (CSF) from perpetators with (ALC-PERP)and without (PERP) a diagnosis of alcoholism and healthy comparison subjects. Compared to controls, ALC-PERP had significantly higher CSF testosterone concentrations, and PERP had significantly lower CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA). These findings lead to the following conclusions: 1) there may be biological differences between perpetrators with and without alcoholism; 2) both low serotonin and high testosterone may have a role in facilitating the fear-related aggression displayed by perpetrators. Additional CSF neurotransmitters are currently being assayed.We performed FDG PET scans on ALC-PERP, non-violent alcoholics, and healthy comparison subjects. Preliminary results show that ALC-PERP have lower glucose metabolism in the right hypothalamus compared to non-violent alcoholics and healthy comparison subjects. To study autonomic regulation in perpetrators, we performed an orthostatic challenge. The strong association between respiratory sinus arrhythmia and heart rate present in controls was not present in the perpetrators. This suggests that perpetrators may have a disturbance in their autonomic function. To study noradrenergic function in perpetrators, we administered the alpha-2-antagonist, yohimbine, to perpetrators and controls. We are in now in the process of having the plasma, which was obtained during the challenge, assayed for various noradrenergic parameters.